Sofa dermatitis: Value of patch test with 2-(thiocyanomethylthio)benzothiazole.

BACKGROUND: In 2008, numerous cases of allergic contact dermatitis caused by leather chairs (sofa dermatitis) were reported, with dimethylfumarate being the culprit allergen. However, octylisothiazolinone, methylisothiazolinone and cobalt have also been associated with cases of sofa dermatitis. An antifungal agent, 2-(thiocyanomethylthio)benzothiazole (TCMTB), has also previously been described as a contact allergen in leather. MATERIALS AND METHODS: Seven patients were referred to the Department of Dermatology of the Cliniques universitaires Saint-Luc, Brussels, Belgium with suspicion of allergic contact dermatitis caused by leather sofas. They were patch tested with the European Baseline Series, additional series (according to the patients' history and clinical aspect of the eruption), dimethylfumarate (4/7 patients) and with TCMTB. RESULTS: All seven patients presented a positive reaction to TCMTB and only one presented a concomitant positive reaction to dimethylfumarate. All patients showed clinical improvement after avoiding contact with their leather sofa. CONCLUSION: 2-(Thiocyanomethylthio)benzothiazole (TCMTB) is probably an underestimated allergen present in leather chairs (responsible for the so-called 'sofa dermatitis'), and more generally in leather objects. It is, therefore, important to test with TCMTB 0.1% petrolatum in case of contact dermatitis related with leather products.

Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants.

BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

Evolution of methylisothiazolinone sensitization: A Belgian multicentric study from 2014 to 2019.

BACKGROUND: In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018. OBJECTIVES: To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. METHODS: A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals. RESULTS: Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT. CONCLUSIONS: Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe. Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.

Adverse cutaneous reaction to diabetic glucose sensors and insulin pumps: Irritant contact dermatitis or allergic contact dermatitis?

BACKGROUND: Adverse cutaneous reactions to diabetes medical devices (glucose sensors and insulin pumps) are described, notably allergic contact dermatitis (ACD) with isobornyl acrylate (IBOA) and N,N dimethylacrylamide (DMAA) as the main allergen. OBJECTIVES: To determine if all cases of adverse cutaneous reactions observed with diabetes medical devices (ie FreeStyle Libre, Enlite sensors or insulin pumps), referred to our department with suspected allergies are confirmed as ACD. PATIENTS AND METHODS: Fifty-two patients who presented skin reactions to diabetes medical devices were patch tested with the European baseline series, a plastic and glues series, a (meth) acrylates series, a piece of the adhesive part of the device, as well as IBOA 0.1% and DMAA 0.1% pet. RESULTS: Seventeen patients had no positive reaction to IBOA nor to the adhesive part of the device; 11 of these also tested with DMAA with negative result. No other relevant allergen was identified. CONCLUSION: Some cutaneous reactions, otherwise very similar to those of patients sensitized to IBOA, can be explained either by the presence of an untested allergen not yet discovered, or by irritant contact dermatitis. Therefore, European legislation on the full labelling of ingredients by manufacturers, in order to facilitate the identification of allergens and irritants, is imperative.

Contact dermatitis caused by glucose sensors in diabetic children.

BACKGROUND: Allergic contact dermatitis caused by glucose sensors has been recently described in diabetics, mostly in adult patients. Isobornyl acrylate and N-N dimethylacrylamide are the potent causative agents. OBJECTIVES: To describe a child population with contact dermatitis caused by glucose sensors, determine the causative allergen, and assess the prevalence of isobornyl acrylate (IBOA) sensitization. PATIENTS AND METHODS: Overall, 12 children with a reaction to medical devices, either glucose sensors or insulin sets, were patch tested with the European baseline series, glues and rubber, (meth) acrylates series, and with piece of the adhesive part of the glucose sensor FreeStyle Libre. Isobornyl acrylate 0.1% pet. was patch tested in 11 patients, and N-N dimethylacrylamide in two. Some patients were tested with adhesive parts of the infusion set. RESULTS: Overall, 10 children reacted to the adhesive part of the sensor FreeStyle Libre, and 10 children were sensitized to IBOA. One patient turned out to be negative in all patch tests. CONCLUSION: Allergic contact dermatitis caused by glucose sensors is common in the pediatric diabetic patient population. Like in the adult patient population, IBOA was the culprit allergen, with 83.3% sensitization prevalence in children exhibiting adverse cutaneous reactions caused by FreeStyle Libre.

Allergic contact dermatitis caused by synthetic rubber gloves in healthcare workers: Sensitization to 1,3-diphenylguanidine is common.

BACKGROUND: The frequency of allergic contact dermatitis has significantly increased in healthcare workers since the transition from latex to synthetic rubber gloves, with 1,3-diphenylguanidine being identified as the most frequently implicated allergen. OBJECTIVES: To highlight the role of 1,3-diphenylguanidine as the culprit allergen in contact allergies to synthetic rubber gloves, to propose recommendations for patch testing, and to discuss alternatives for sensitized subjects. MATERIALS AND METHODS: Patch test data from healthcare workers who developed hand dermatitis after wearing rubber gloves and who reacted positively to glove samples and rubber additives were collected from September 2010 to December 2017 in a Belgian hospital. RESULTS: A total of 44 caregivers were included in this study. Patch tests showed that: (a) 84% of the study population reacted positively to carba mix; (b) 86% reacted positively to 1,3-diphenylguanidine; and (c) 13 (30%) reacted positively to thiuram mix. Half of the subjects reacted positively to gloves containing 1,3-diphenylguanidine, whereas none reacted to accelerator-free gloves. CONCLUSION: The most commonly identified allergen was 1,3-diphenylguanidine, far ahead of thiurams, which were previously described as the most sensitizing accelerators. The use of 1,3-diphenylguanidine-free gloves is recommended. No subject reacted to gloves without accelerators, thus confirming their efficiency among accelerator-sensitized patients. We recommend that 1,3-diphenylguanidine be added to the European baseline series.

Allergic contact dermatitis caused by isobornyl acrylate in the Enlite glucose sensor and the Paradigm MiniMed Quick-set insulin infusion set.

BACKGROUND: The FreeStyle Libre glucose sensor has caused many cases of allergic contact dermatitis, and isobornyl acrylate (IBOA) in this sensor has been identified as one of the culprit allergens. OBJECTIVES: To report on the presence of IBOA in devices produced by Medtronic, namely, the Enlite sensor and the insulin infusion set Paradigm MiniMed Quick-set. PATIENTS AND METHODS: Five patients reacting to the glucose sensor Enlite and/or the insulin infusion set Paradigm MiniMed Quick-set observed in three clinics (two Belgian and one Swedish) were patch tested with the baseline and other series, as well as with IBOA; four of them also with pieces of adhesive patches from the devices, and two with a thin layer chromatogram of Enlite glucose sensor extracts. Gas chromatography-mass spectrometry (GC-MS) analyses were performed. RESULTS: Four patients reacted to IBOA and one to colophonium, a known allergen in Enlite, and three to the adhesive part of the sensor or the insulin infusion set. IBOA was identified in the sensor by GC-MS, and its presence was indicated in the infusion set. CONCLUSIONS: IBOA is a contact allergen in Enlite glucose sensor, and likely also in the infusion set. Therefore, these devices are not suitable alternatives for patients sensitized to the FreeStyle Libre sensor.

The preservative 2-(thiocyanomethylthio)benzothiazole: A potential allergen in leather products.

BACKGROUND: Allergic contact dermatitis caused by leather is common, and several responsible allergens, such as tanning agents, glues, mercaptobenzothiazole derivatives, and dyes, but also antimicrobials and antifungals, are involved. MATERIAL AND METHODS: Three female patients were referred to the Departments of Dermatology in a Belgian university hospital following skin reactions caused by leather products (shoes, belt, and car seats). They were patch tested with the European baseline series and samples of suspected leather products, and additionally with 2-(thiocyanomethylthio)benzothiazole (TCMTB), an antifungal agent previously reported to be a contact allergen in footwear. Chromatographic analyses of samples of all the leather materials tested were performed at the Department of Occupational and Environmental Dermatology in Malmö, Sweden. RESULTS: The patients reacting to the leather samples were shown to be sensitized to TCMTB, the presence of which could be confirmed by chemical analyses of samples obtained from the patients. CONCLUSION: Patch tests with TCMTB should be considered in patients with contact dermatitis caused by leather items.

N,N-dimethylacrylamide-A new sensitizer in the FreeStyle Libre glucose sensor.

BACKGROUND: Isobornyl acrylate (IBOA) has recently been identified as one sensitizer in the FreeStyle Libre glucose sensor. Analyses with gas chromatography-mass spectrometry (GC-MS) have indicated the presence of N,N-dimethylacrylamide (DMAA) in the sensor. MATERIAL AND METHODS: Seven patients were referred for patch testing after developing skin reactions when using FreeStyle Libre. All patients were patch tested with IBOA and DMAA. Two patients were tested with adhesive patches that had been removed from the sensors "as is," and two patients were tested with acetone extracts of materials from the sensor. The extracts were analysed with GC-MS. RESULTS: Six patients reacted to both IBOA and DMAA, and one patient reacted only to DMAA. Positive reactions were also observed in both patients tested with the adhesive patch "as is". One patient reacted to both an extract of the adhesive patch and an extract of the sensor itself. When analysed with GC-MS, IBOA was found in both extracts and DMAA was found in the extract of the sensor. CONCLUSION: Both IBOA and DMAA may be present in adhesives used in medical devices such as glucose sensors or insulin pumps, and should be patch tested when suspected contact allergic reactions to these products are investigated.

Unexpected positive patch test reactions to sesquiterpene lactones in patients sensitized to the glucose sensor FreeStyle Libre.

BACKGROUND: Most diabetic patients sensitized to FreeStyle Libre react to isobornyl acrylate (IBOA), with a considerable number of them also showing unexpected positive patch test reactions to sesquiterpene lactone (SL) mix (SLM) tested in the baseline series. OBJECTIVES: To compile patch test results of subjects affected, and provide potential explanations for this association. PATIENTS AND METHODS: Fifty-three Freestyle Libre-allergic patients were patch tested with IBOA and/or SLM, and several were also patch tested with the components of SLM. Chromatographic analyses were performed on the glucose sensor, IBOA, and the components of SLM. RESULTS: Thirty-three patients reacted positively to the components of SLM, and 11 of 27 patients reacted positively to alantolactone, in particular. Gas chromatography-mass spectrometry (GC-MS) analyses did not detect these chemicals in the different parts of the glucose sensor, or in IBOA. CONCLUSION: Significant co-sensitizations between SLs on the one hand and the glucose sensor FreeStyle Libre and/or isobornyl acrylate on the other hand exist, without evidence of the presence of SLs via GC-MS analysis. Cross-reactions between them seem improbable. As a possible hypothesis, a common precursor for both, such as camphene, may exist.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs: Two case reports and a review of the literature.

BACKGROUND: Patients suffering from drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by first-line antituberculosis drugs often need to be retreated rapidly. Patch tests prior to the reintroduction of antituberculosis drugs are rarely performed. OBJECTIVES: To highlight those drugs most often involved in DRESS caused by antituberculosis drugs, illustrate the potential value of patch tests to identify these culprit(s), and provide insights into how to rapidly retreat these patients. METHODS: A detailed description of the work-up of two illustrative patients, together with a literature review of similar cases, is provided. RESULTS: All first-line antituberculosis drugs may cause DRESS syndrome, but rifampicin and isoniazid are most frequently involved. Patch tests can be performed sooner than usually advised in the context of DRESS syndrome, and potentially with lower test concentrations, but false-negative results are possible. Sequential reintroduction of patch test-negative drugs is feasible, although the dose and order of drugs to be readministered, as well as the use of concomitant systemic corticosteroids, remain a matter of debate. CONCLUSION: Patch tests in the context of DRESS syndrome caused by antituberculosis drugs, despite their shortcomings, may potentially guide rapid retreatment of these patients.

Treatment of chronic spontaneous urticaria: Immunomodulatory approaches.

This paper summarizes and reviews the mechanisms of action and data concerning efficacy of recommended treatments as well as other treatments that have been tested, independently of the outcomes, in the management of chronic spontaneous urticaria. Due to the central role of mast cells, basophils and histamine in the pathophysiology of this disease, H1-antihistamines remain the first-line treatment. However, current knowledge about this complex disease, also recognizes an important role for T lymphocytes, B lymphocytes, and autoantibodies. Implications of these others mediators thus provide further targets for treatment. Indeed, agents previously used to treat other autoimmune and inflammatory diseases, have demonstrated efficacy in chronic spontaneous urticaria and are therefore potential therapeutic alternatives for antihistamine unresponsive patients.

Allergic contact dermatitis caused by medical devices for diabetes patients: A review.

Allergic contact dermatitis caused by medical devices for diabetes patients has been increasingly described in the literature in the last few years. This article reviews the cases of allergic contact dermatitis caused by insulin pumps and glucose sensors reported since the 1970s, the culprit allergen(s), the results of patch tests and/or chromatographic analysis, and preventive measures.

Increased expression of interleukin-9 in patients with allergic contact dermatitis caused by p-phenylenediamine.

BACKGROUND: Allergic contact dermatitis has been described as a type IV reaction caused by antigen-specific T cells. Central roles for CD8+ cytotoxic T cells as effector cells and CD4+ T cells as regulatory cells have been suggested. T helper (Th) 2 and Th1 cytokines have been implicated; however, the nature of the allergen influences the Th response. OBJECTIVE: To determine the types of T cells and cytokines expressed in patients allergic to p-phenylenediamine (PPD). METHODS: Serial skin biopsies of areas with positive patch test reactions in 29 PPD-sensitized patients were collected. T cell markers and cytokine expression were analysed by flow cytometry and quantitative reverse transcription polymerase chain reaction in both skin and peripheral blood mononuclear cells (PBMCs) of sensitized patients. RESULTS: We observed increased expression of T cell markers and Th2/Th9-associated cytokines in both skin and stimulated PBMCs of PPD-allergic patients. Moreover, interleukin (IL)-9 was mainly produced by Th9 cells, in both skin and PBMCs. Further investigations showed that Il9r-deficient mice were more affected in a PPD contact hypersensitivity model than wild-type mice. CONCLUSION: We did not confirm the preclinical presence of CD8+ T cells. However, the expression of different T cell markers positively correlated with patch test reactions. IL-9 expression was strongly upregulated and directly related to patch test severity. In addition, we showed that IL-9 has an anti-inflammatory role in a mouse model of PPD contact hypersensitivity.

Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor.

BACKGROUND: Glucose sensors, such as FreeStyle® Libre, are innovative medical devices developed for diabetes patients as a replacement for classic glucose meters, ensuring continuous glucose monitoring without the disadvantage of regular skin finger pricks. OBJECTIVES: To report several cases of allergic contact dermatitis caused by FreeStyle® Libre, and to report on isobornyl acrylate as a culprit allergen. PATIENTS AND METHODS: Fifteen patients presented with allergic contact dermatitis caused by FreeStyle® Libre. All but 1 were patch tested with a baseline series, and with pieces and/or ultrasonic bath extracts of (the adhesive part of) the glucose sensor. Isobornyl acrylate was patch tested, in various concentrations and vehicles, in 13 patients. Gas chromatography-mass spectrometry (GC-MS) of the sensors was performed. RESULTS: All patients reacted to the adhesive part of the sensor, and 12 patients were shown to be sensitized to isobornyl acrylate. Simultaneous reactions to other allergens were rarely observed. GC-MS showed the presence of isobornyl acrylate in the sensors. CONCLUSIONS: Cases of allergic contact dermatitis caused by FreeStyle® Libre are increasingly being observed, and isobornyl acrylate is a relevant culprit allergen. Cross-reactivity to other acrylates was infrequently observed, but other, hitherto unidentified, contact allergens may still be present in the device.